Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is highly enriched in the central nervous system, and is proposed to play important roles in activity-dependent modifications of neuronal functions. We reported previously on the dynamic regulation of the autonomous CaMKII in homogenates from hippocampus and parietal cortex by acute neuronal excitation induced by electroconvulsive treatment (ECT) in rats in vivo. In the present study, we examined in more detail the biochemical changes in CaMKII under such conditions. We unexpectedly found a concurrent increase in autophosphorylation at Thr286(alpha)/287(beta) and decrease in the specific activity of CaMKII in the particulate fraction in either hippocampus or parietal cortex during ECT-induced acute, brief seizure activity. On the other hand, the soluble CaMKII showed a marked decrease in autophosphorylation with unchanged or rather increased specific activity. Increased autophosphorylation and decreased CaMKII activity were associated with the detergent-insoluble particulate fraction. All these changes disappeared soon after the termination of seizure activity. The reversible formation of such an autophosphorylated, inactivated and sedimentable form of CaMKII during acute neuronal excitation may indicate the existence of a novel regulatory mechanism of CaMKII that may be important for normal functioning of the brain.